rs146704427

Variant names:

• chr12-6977385-C-G
• rs146704427
• NM_005768.6:c.1329G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-6977385-C-G
• chr12-6977385-C-A
• chr12-6977385-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005768.6(LPCAT3):​c.1329G>C​(p.Thr443Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: LPCAT3 NM_005768.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.46
• Publications: 1 publications found

Genes affected

LPCAT3 (HGNC:30244): (lysophosphatidylcholine acyltransferase 3) Enables 1-acylglycerophosphocholine O-acyltransferase activity; 1-acylglycerophosphoethanolamine O-acyltransferase activity; and 1-acylglycerophosphoserine O-acyltransferase activity. Involved in phosphatidylcholine acyl-chain remodeling; phosphatidylethanolamine acyl-chain remodeling; and phosphatidylserine acyl-chain remodeling. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

EMG1 (HGNC:16912): (EMG1 N1-specific pseudouridine methyltransferase) This gene encodes an essential, conserved eukaryotic protein that methylates pseudouridine in 18S rRNA. The related protein in yeast is a component of the small subunit processome and is essential for biogenesis of the ribosomal 40S subunit. A mutation in this gene has been associated with Bowen-Conradi syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

EMG1 Gene-Disease associations (from GenCC):

• Bowen-Conradi syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000290146 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-6977385-C-G is Benign according to our data. Variant chr12-6977385-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3777872.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005768.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT3	NM_005768.6	MANE Select	c.1329G>C	p.Thr443Thr	synonymous	Exon 11 of 13	NP_005759.4
	EMG1	NM_006331.8	MANE Select	c.*1576C>G		3_prime_UTR	Exon 6 of 6	NP_006322.4
	EMG1	NM_001320049.2		c.*1576C>G		3_prime_UTR	Exon 5 of 5	NP_001306978.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT3	ENST00000261407.9	TSL:1 MANE Select	c.1329G>C	p.Thr443Thr	synonymous	Exon 11 of 13	ENSP00000261407.4	Q6P1A2-1
	EMG1	ENST00000599672.6	TSL:1 MANE Select	c.*1576C>G		3_prime_UTR	Exon 6 of 6	ENSP00000470560.1	Q92979
	LPCAT3	ENST00000535479.5	TSL:1	n.*952G>C		non_coding_transcript_exon	Exon 9 of 11	ENSP00000438765.1	F5H0M4

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000382 AC: 96 AN: 251386 AF XY: 0.000317

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000426 AC: 623 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.000426 AC XY: 310 AN XY: 727246

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000783 AC: 35 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000509 AC: 566 AN: 1112010

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74444

African (AFR) AF: 0.0000481 AC: 2 AN: 41558

American (AMR) AF: 0.00170 AC: 26 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000264 Hom.: 0

Bravo AF: 0.000484

EpiCase AF: 0.000763

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0040
DANN	Benign	0.71
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146704427; hg19: chr12-7086547;